PROJECT SUMMARY The proposed experiments aim to determine how the consequences of asymmetric hearing loss (AHL) in auditory cortex affect the neural processes that allow listeners to parse and decode foreground sounds in background noise. AHL is one of the most common forms of hearing impairment, and it profoundly disrupts spatial hearing and the ability to process signals in noise (SIN). Disabilities across hearing domains are generally more severe in AHL patients than in equivalent cases of symmetric sensorineural hearing loss (SNHL). Thus, AHL has broad implications for health, including tinnitus, cognitive impairment, and reduced quality of life. We recently discovered that the cortical hemispheres ipsilateral and contralateral to the hearing loss recover differently after asymmetric acoustic trauma. Specifically, spectral preferences for sounds emanating from the two ears realign in the contralateral hemisphere within ~6 months after AHL but remain misaligned in the ipsilateral hemisphere. Neither the dynamics nor the functional consequences of these hemispheric differences on SIN processing or crucial auditory functions such as central gain adaptation are known. Furthermore, we recently discovered that neurons in normal auditory cortex are considerably diverse in how well they tolerate background noise. Some neurons actually improving their processing in the presence of noise. This diversity creates an opportunity to identify the factors that determine the noise tolerance of cortical neurons and the consequences of AHL. We propose to conduct a multifaceted, longitudinal analysis of bilateral cortical reorganization following AHL. The role of inhibitory interneurons is of special interest because inhibitory dysregulation has been implicated as both a cause and consequence of hearing loss. Our Aims will determine (1) how AHL affects the sensitivity to background sounds in the cortical circuits, (2) how AHL affects the ability of cortical neurons to adapt to changes in stimulus level and contrast, and (3) how functional changes in AHL relate to the structural and functional expression of inhibition in cortical networks. We will estimate spectral and temporal tuning properties, excitatory-inhibitory balance, and temporal context capabilities, which are all critical for optimal speech perception. We will provide the first examination of disrupted cortical SIN processing in AHL by studying monaural and binaural signal decoding abilities over a range of competing background noise levels. We will relate the degree and time course of AHL-induced functional processing changes to neuroanatomically determined alterations in the interneuron density across core cortical fields in the two hemispheres. The wealth of new insights generated by this approach will resolve numerous outstanding questions regarding central reorganization in AHL and its dynamic time course, equip clinical researchers with new and better-defined central biomarkers of AHL, facilitate the development of improved rehabilitation strategies, and provide a new way to understand how the brain extracts signals from noise in normal and impaired hearing.